Chronic Kidney Disease - Identification, Evaluation and Management of Patients
Effective Date: September 15, 2008
Full Guideline in PDF
Recommendations and Topics
The first part of this guideline provides recommendations for the investigation and evaluation of adult patients (19+) at risk for chronic kidney disease (CKD). The second part of this guideline focuses on the management of adult patients with known CKD and includes care objectives and patient self-management.
Specialized management of established CKD, e.g. erythropoietic agents for anemia, renal replacement therapy, and treatment of calcium, phosphate, or parathyroid hormone (PTH) abnormalities is beyond the scope of this guideline.
Diagnostic Code: 585 (chronic renal failure)
Part 1: Identification and Evaluation of Patients at Risk for CKD
This section covers:
- Prevention and risk factors
- Diagnosis and staging of CKD
- Determining the cause of CKD
- Evaluating patients with abnormal screening tests
- Flow diagram for evaluating and managing suspected CKD
I. Prevention and risk factors
Identify patients at risk for CKD based upon a directed medical and surgical history including co-morbidities (e.g. diabetes, cardiovascular disease [CVD]) and dietary, social, demographic and cultural factors, a review of symptoms, and physical examination. Populations at increased risk include those with:
- Hypertension with or without CVD
- A family history of kidney disease
- Specific high-risk ethnic groups: First Nations, Pacific Islanders, African descent and Asians
Note: Age > 60 years is associated with an increased risk of impaired kidney function, but evidence is insufficient to recommend screening solely on the basis of age.
It is recommended that physicians screen at-risk populations every 1-2 years depending upon clinical circumstances (e.g. yearly for persons with diabetes) using serum creatinine and random urine tests (macroscopic/microscopic urinalysis and ACR). Estimated glomerular filtration rate (eGFR) is the best marker for CKD and is computed from the serum creatinine. Most labs in
British Columbia (BC) automatically report eGFR when a serum creatinine is ordered. (See Appendix B for further information on eGFR calculations.)
a)Serum testing: eGFR values:
- < 60 mL/min and persistent (present for > 3 months) indicates substantial reduction in kidney function.
- > 60 mL/min and < 100 mL/min, in the absence of urine abnormalities or structural abnormalities on imaging studies (e.g. ultrasound), does not indicate kidney disease.
- Age > 75 years: accuracy of eGFR for patients over 75 is questionable and may underestimate true kidney function. Values of eGFR < 45 should be considered as a likely indicator of decreased renal function and merit further work-up. Values between 45 and 60 may reflect normal variation in the absence of other conditions, however, caution is still recommended with respect to medications, dye, and risk of acute kidney injury with severe illnesses. Correlation with clinical condition is recommended.1
- Age > 85 years: equation for eGFR is problematic and risk of progression of CKD is not known. In the absence of other metabolic or hematological abnormalities, a conservative approach is recommended. Values between 45 and 60 may reflect normal variation in the absence of other conditions. Caution is still recommended with respect to medications, dye, and risk of acute kidney injury with severe illnesses.
- Estimates based on serum creatinine measurements (eGFR) may be unreliable in patients with very large or small body habitus, those on specific diets (very high or very low protein), and in patients receiving medications that interfere with the excretion of creatinine (e.g. trimethoprim and sulfamethoxazole, ciprofloxacin, fenofibrate).
- Exercise, diet and/or hydration status may affect kidney function estimates or the degree of albuminuria/proteinuria. If baseline tests are abnormal or subsequent tests are significantly different from baseline, confirmation by repeat testing is warranted.
b)Urine testing: macroscopic/microscopic analysis and albumin/creatinine ratio (ACR) values
- Random urine tests for macroscopic/microscopic urinalysis and ACR:
- Significant abnormalities: persistent white blood cells or red blood cells in the absence of infection or instrumentation; presence of any cellular casts is always pathological.
- ACR elevation (> 2.0 mg/mmol males; > 2.8 mg/mmol females) on 2 out of 3 serial tests performed 1 week to 2 months apart indicates micro-vascular disease +/- glomerular disease.
- Urine test abnormalities, even with persistent eGFR values ≥ 60 ml/min, indicate abnormal kidney function, either as an isolated condition or as a symptom of a systemic disease.
- 24-hour urine collections are not necessary in most cases.
- ACR is the method that allows one to test for albumin present in quantities above normal but below the detectable range on standard dipsticks. In the past, the word microalbumin has been used, but this may lead to a false impression that there is a different molecule when there is not. Thus, ACR is the preferred method by which to assess abnormal levels of albumin. Note that this guideline uses the thresholds adopted by the Canadian Diabetes Association for the detection of microalbuminuria. As methods improve and further data becomes available, these cutoffs may be revised. Serial ACR tests can normally be incorporated into the routine visit schedule.
Acting on test results
- Normal: repeat annually or as clinically indicated and monitor blood pressure.
- Abnormal: confirm and evaluate (Table 1 below).
III. Diagnosis and staging of CKD
CKD is defined as eGFR < 60 mL/min for > 3 months, or evidence of kidney damage (pathologic abnormalities or markers of damage, including abnormalities in blood or urine tests or imaging studies). If CKD is present, determine its stage based on eGFR, urinalysis, and ACR. The following staging system, designed by the US National Kidney Foundation with international input, is recommended to facilitate assessment and management of CKD.2,3
Table 1. Stages of CKD
IV. Determining the cause of CKD
Impaired kidney function is often multi-factorial. If possible, determine a primary cause of kidney disease in all patients. Kidney ultrasound is a useful examination to identify polycystic kidney disease, cancer, stones, and obstruction. Discrepancy in kidney size may signal clinically significant renal artery stenosis (the work up for renal artery stenosis is beyond the scope of this guideline).
Even if a primary cause seems obvious (e.g. hypertension, diabetes), the possibility of a serious underlying disorder (e.g. vasculitis, systemic lupus erythematosis) must be considered in patients with:
- Abnormal urinalysis, e.g. proteinuria, hematuria, cellular casts, or combinations thereof.
- Rapid sustained decline in kidney function (ΔeGFR > 10-15%/year) despite remedy of reversible precipitants e.g. volume contraction, febrile illness, medications.
- Consistent impairment of kidney function in the absence of risk factors.
- Constitutional symptoms suggesting systemic illness.
- Sudden or severe onset of symptoms, e.g. edema unrelated to heart or liver disease.
Refer to an internist or nephrologist for further evaluation if an etiology cannot be determined. Note that occasionally a screening test will identify a serious systemic disease or early stages of an acute illness. In patients with active urine sediments (rbc casts or cellular casts ± protein), constitutional symptoms, or unexplained severity of kidney dysfunction, prompt consultation with a specialist and/or re-evaluation of tests is indicated.
V. Evaluating patients with abnormal screening tests
Patient management should reflect CKD stage and eGFR, urinalysis and ACR results (see Table 2).
Table 2. Evaluating patients with abnormal screening testsa
Figure 1. Flow Diagram for Evaluating and Managing Patients with Suspected CKD
Part 2: Management of Patients with Established CKD
This section covers:
- Identifying care objectives and targets
- Practice points for goal setting
- Supporting patient self-management
- Meeting care objectives
I. Identifying care objectives and targets
Physicians will ideally identify care objectives for all patients with CKD (see Table 3). Depending on the level of kidney function and complexity of therapy required, these care objectives may be more or less difficult to achieve without help from a specialized team of health care professionals including a nephrologist. Treatment goals must be tailored to the individual.
Table 3: Care objectives and targets
II. Practice points for goal setting
When setting goals with your patient, consider the following:
- Exercise, diet, and/or hydration status may affect kidney function estimates or the degree of albuminuria/proteinuria. If baseline tests are abnormal or subsequent tests are significantly different from baseline, confirm by repeat testing.
- Rigorous control of BP has been shown to reduce the risk of complications and mortality rates. In particular, the inhibition of the renin angiotensin system with ACE inhibitors or ARBs has been shown to be very effective. Diuretics, ß-blockers, and/or calcium channel blockers may also be required since most patients require more than two medications to reach target values.9 See BC guideline: Hypertension - Detection, Diagnosis and Management.
- Every adult with kidney disease may be at increased risk of cardiovascular disease.4,10
- Nephrotoxic medications (e.g. NSAIDs, COX-2 inhibitors, aminoglycosides) should be avoided or used with caution in patients with even mild kidney impairment (eGFR 60-90 mL/min with evidence of kidney damage), and kidney function should be monitored if they are used.
- IV or intra-arterial radiocontrast use poses a high risk of acute kidney injury in patients with Stage 4 or 5 CKD and a moderate risk in patients with Stage 3 disease.11 If imaging is required, alternate imaging techniques, including MRI angiography, should be considered for these patients. If no alternative exists and the procedure is medically necessary, the patient should provide written informed consent and protection with IV hydration and N-acetyl cysteine may be used according to a published protocol, or in consultation with nephrologists.12
- Patients with CKD are at high risk of further acute kidney injury with volume contraction, e.g. nausea, vomiting, diarrheal illnesses, or the use of certain bowel preparations.
- Review medication list, identify medications excreted by the kidneys (e.g. metformin, digoxin and lithium) and adjust dosages as appropriate or use alternate treatment.13 (see Physician's Resource section).
- Rapid deterioration in kidney function (a decline of eGFR >10-15% annually) warrants urgent referral to a nephrologist or internist.
- Preparation for kidney replacement treatment requires a minimum of 12 months, therefore referral for consideration of kidney replacement should take this into account.
- Many patients with CKD also have diabetes and/or heart disease. Explaining the linkage between these conditions and how treating one condition benefits others may lessen the psychological impact of several separate diagnoses.14
III. Supporting patient self-management
People with CKD have better outcomes if they take an active role in the management of their own condition and they should be encouraged to do so. Denial, often associated with grief reaction, is common in patients with chronic disease affecting a vital organ. Efforts to introduce preventive lifestyle and medical therapy may fail until understanding and acceptance have been achieved. CKD care teams are skilled at dealing with this issue.
To support patient self-management, the physician should:
- Support patients through the process of accepting the diagnosis of a chronic illness.
- Ensure that patients understand the implications of the diagnosis and their role in self- management.
- Help patients identify a support team.
- Involve patients in defining the best possible goals for care, including lifestyle modifications such as smoking cessation, healthy diets, weight management, exercise, and social support.
- Encourage patients to monitor their own progress through the use of diaries or logbooks to track clinical values, and self-monitor BP (and blood glucose where appropriate).
- Reinforce lifestyle modifications at each visit.
- Explain and discuss the results of investigations and consultations.
- Identify community resources that can provide patients with the information, skills and support needed to understand and manage their condition, and direct or refer patients to those resources.
- Patient self-management resources are listed inChronic Kidney Disease: A Guide for Patients,are available at www.BCGuidelines.ca
IV. Meeting care objectives
The care of CKD patients is very similar to care of any patient with a chronic illness, thus similar principles should be applied. Evidence indicates that the care of chronic diseases such as CKD can be improved by the implementation of regular scheduled reviews of clinical and laboratory parameters.
Physicians are encouraged to:
- Create a patient register to identify all patients with impaired kidney function in their practice.
- Participate in a community or provincial patient register wherever possible.
- Use a flow sheet for each patient with kidney disease. (See Appendix C for sample flow sheet.)
- Use an organized recall system to ensure that laboratory investigations and subsequent office reviews are performed at regularly scheduled appropriate intervals.
- Review patient records to ensure care objectives are met.
There is increasing evidence that at lower levels of eGFR, patients benefit from inclusion in multidisciplinary clinics. It is recommended that primary care physicians seek opportunities within their communities to ensure these resources are accessed.15,16,17
This guideline outlines strategies that may help the primary care practitioner meet the complex needs of persons with CKD, including accurate and timely diagnosis, exploration of its etiology, and appropriate management of common factors affecting progression and co-morbid conditions.
CKD is a serious population health problem with a significant impact on individuals, families, society, and health services. It is often associated with other common chronic diseases such as diabetes, hypertension, and heart disease. Based on population studies, the estimated prevalence of significant kidney impairment (eGFR < 60 ml/min) in British Columbia is 145,000 people, approaching the prevalence of Type II diabetes; however, because many cases are undiagnosed, this is likely a true significant underestimate.
There is increasing awareness of CKD in all practices.18 CKD increases the risk of cardiac morbidity and mortality to levels ten times that of population mean risk in addition to placing persons at risk of end stage renal disease requiring dialysis.19,20 Recent studies have demonstrated that the presence of impaired kidney function worsens prognosis for length of hospital stay, morbidity, and mortality.4,10,21,22,23 Thus, while not all people with kidney disease will require dialysis, they are all at higher risk for poor outcomes, adverse reactions to medications and interventions, and episodes of acute kidney failure.4,21,24,25
The outcome of patients who go on to dialysis remains poor with ten per cent annual mortality; the overall five-year survival rate is worse than that of all cancers except cancer of the lung.26 Evidence clearly indicates that efforts to control hypertension and proteinuria (and hyperglycemia in persons with diabetes) can prevent or postpone the development of progressive kidney function decline.7,8,27,28,29,30,31,32,33,34 However, levels of care for milder stages of CKD remain suboptimal and practitioners often do not provide screening and management in accordance with published guidelines.35,36,37
The efficacy of statins in a population with CKD is currently under evaluation in the SHARP trial.38 Until the results are reported, basic risk reduction approaches are recommended as provided in the BC clinical practice guideline,Cardiovascular Disease - Primary Prevention.39 For people without heart disease, a Framingham risk-based approach to treatment with statins is suggested for people with a ten-year coronary heart disease (CHD) risk of 20% or more. Treatment of the high risk population should be to an LDL target of 2.5 mmol LDL/L or a ratio of TC/HDL of < 4.
The BC clinical practice guideline, Diabetes Care, recommends a risk-based approach for lipid management with treatment to an LDL target of 2.5 mmol/L for high-risk patients (> 20 % CHD risk using the UKPDS calculator).40 This approach is consistent with the recent ASPEN trial which showed no benefit using statins for people with low to moderate risk of CHD (low risk, 12% smokers)41 and the CARDS trial, which showed a benefit for population at higher-risk (23% smokers).42 For elderly patients (70+ years), the PROSPER trial found that statins did not reduce CHD and stroke events in men and women without CHD.43
- Gill J, Malyuk R, Djurdjev O, et al. Use of GFR equations to adjust drug doses in an elderly multi-ethnic group - a cautionary tale. Nephrol Dial Transplant 2007;22(10):2894-9.
- National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39(2) Suppl 1:S1-266.
- Levey AS, Atkins R, Coresh J, et al. Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from Kidney Disease Improving Global Outcomes. Kidney Int 2007;72(3):247-59.
- Sarnak MJ, Levey AS, Schoolwerth AC, et al. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 2003;108(17):2154-69.
- Levin A, Bakris G, Molitch M, et al. Prevalence of abnormal serum vitamin D, PTH, calcium and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int 2007;71:31-8.
- Da Roza G, Loewen AHS, Djurdjev O, et al. Stage of CKD predicts seroconversion after hepatitis B immunization: earlier is better. Am J Kidney Dis 2003;42(6):1184-92.
- Trivedi HS, Pang MM, Campbell A, et al. Slowing the progression of chronic renal failure: economic benefits and patients perspectives. Am J Kidney Dis 2002;39:721-9.
- Coyle D, Rodby R, Soroka S, et al. Cost-effectiveness of irbesartan 300 mg given early versus late in patients with hypertension and a history of type 2 diabetes and renal disease: a Canadian perspective. Clin Ther 2007;29(7):1508-23.
- Guidelines and Protocols Advisory Committee. Hypertension - Detection, Diagnosis and Management. [Clinical Practice Guideline]. Available from www.BCGuidelines.ca. Accessed August12, 2008.
- Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events and hospitalization. N Engl J Med 2004;351(13):1296-305.
- Tepel M, van der Giet M, Schwarzfeld C, et al. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med 2000;343(3):180-4.
- Komenda P, Zalunardo N, Burnett S, et al. Conservative outpatient renoprotective protocol in patients with low GFR undergoing contrast angiography: a case series. Clin Exp Nephrol 2007;11(3):209-13.
- Kappel J, Calissi P. Nephrology: 3. Safe drug prescribing for patients with renal insufficiency. CMAJ 2002;166(4):473-7.
- Komenda, P, Levin, A. Analysis of cardiovascular disease and kidney outcomes in multidisciplinary chronic kidney disease clinics: complex disease requires complex care models. Curr Opin Nephrol Hypertens 2006;15(1):61-6.
- Goldstein M, Yassa T, Dacouris N, et al. Multidisciplinary predialysis care and morbidity and mortality of patients on dialysis. Am J Kidney Dis 2004;44(4):706-14.
- Curtis BM, Ravani P, Malberti F, et al. The short- and long-term impact of multi-disciplinary clinics in addition to standard nephrology care on patient outcomes. Nephrol Dial Transplant 2005;20(1):147-54.
- Hemmelgarn BR, Manns BJ, Zhang J, et al. Association between multidisciplinary care and survival for elderly patients with chronic kidney disease. J Am Soc Nephrol 2007;18(3):993-9.
- Stevens L A, Cooper S, Singh S, et al. Detection of chronic kidney disease in non-nephrology practices: an important focus for intervention. BCMJ 2005;47(6):305-11.
- Valmadrid CT, Klein R, Moss SE, et al. The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus. Arch Intern Med 2000;160(8):1093-100.
- Canadian Institute for Health Information. CORR reports - treatment of end-stage organ failure in Canada 1995 to 2004 (2006 Annual Report). 2007 February [132 pages]. Available from http://secure.cihi.ca/cihiweb/dispPage.jsp?cw_page=PG_710_E&cw_topic=710&cw_rel=AR_5_E#full. Accessed August 14, 2008.
- Culleton BF, Larson MG, Wilson PW, et al. Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency. Kidney Int 1999;56(6):2214-19.
- Curtis BM, Parfrey PS. How can the cardiac death rate be reduced in dialysis patients? Semin Dial 2002;15(1):22-24.
- Humphries K, Stigant, C, Levin A, et al. Outcomes after percutaneous coronary interventions in patients with CKD: improved outcome in the stenting era. Am J Kidney Dis 2005;45(6)1002-9.
- Levin A. Prevalence of cardiovascular damage in early renal disease. Nephrol Dial Transplant 2001;16 Suppl 2:7-11.
- Hemmelgarn BR, Zhang J, Manns BJ, et al. Progression of kidney dysfunction in the community- dwelling elderly. Kidney Int 2006;69(12):2155-61.
- Arun CS, Stoddart J, Mackin P, et al. Significance of microalbuminuria in long-duration type 1 diabetes. Diabetes Care 2003;26(7):2144-9.
- Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329(14):977-986.
- Modification of the Diet in Renal Disease Study Group. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease: modification of diet in renal disease study group. N Engl J Med 1994;330(13):877-84.
- Diabetes Control and Complications Trial (DCCT) Research Group. Effect of intensive therapy on development and progression of nephropathy in the DCCT. Kidney Int 1995;47:1703-20.
- Bakris GL. Lower blood pressure goals for patients with diabetes: the National Kidney Foundation consensus report. J Clin Hypertension 2000;369-71.
- Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet 2000;335(9200):253-9.
- RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345(12):851-60.
- Duncan L, Heathcote J, Djurdjev O, et al. Screening for renal disease using serum creatinine: who are we missing? Nephrol Dial Transplant 2001;16(5):1042-6.
- ACE Inhibitors in Diabetic Nephropathy Trialist Group. Should all patients with type I diabetes mellitus receive angiotensin-converting enzyme inhibitors? A meta-analysis of individual patient data. Ann Intern Med 2001;134(5):370-9.
- Valderrabáno F, Golper T, Muirhead N et al. Chronic kidney disease: why is current management uncoordinated and suboptimal? Nephrol Dial Transplant 2001;16 Suppl 7:61-4.
- Powe NR. Early referral in chronic kidney disease: An enormous opportunity for prevention. Am J Kidney Dis 2003;41(2):505-7.
- Stigant C, Stevens L, Levin A. Nephrology: 4. Strategies for the care of adults with chronic kidney disease. CMAJ 2003;168(12):1553-60.
- SHARP Study of Heart and Renal Protection. Clinical trial information available at www.sharpinfo.org Accessed August 14, 2008.
- Guidelines and Protocols Advisory Committee. Cardiovascular Disease - Primary Prevention. [Clinical Practice Guideline]. Available at www.BCGuidelines.ca. Accessed August 14, 2008.
- Guidelines and Protocols Advisory Committee. Diabetes Care. [Clinical Practice Guideline]. Available at www.BCGuidelines.ca. Accessed August 14, 2008.
- Knopp RH, d'Emden M, Smilde JG, et al. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in non-insulin-dependent diabetes mellitus (ASPEN). Diabetes Care 2006;29(7):1478-85.
- Colhoun H, Betteridge DT, Durrington PN, et al. 2004. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004;364(9435):685-96.
- Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360(9346):1623-30.
This guideline is based on scientific evidence current as of the Effective Date.
This guideline was developed by the Guidelines and Protocols Advisory Committee, approved by the British Columbia Medical Association, and adopted by the Medical Services Commission.
Appendix A - Physician Resources
Appendix B - Calculating eGFR: Conversion Table
Appendix C - Chronic Kidney Disease Flow Sheet
Appendix D - Chronic Kidney Disease - A Guide for Patients
The principles of the Guidelines and Protocols Advisory Committee are to:
- encourage appropriate responses to common medical situations
- recommend actions that are sufficient and efficient, neither excessive nor deficient
- permit exceptions when justified by clinical circumstances.
Disclaimer The Clinical Practice Guidelines (the "Guidelines") have been developed by the Guidelines and Protocols Advisory Committee on behalf of the Medical Services Commission. The Guidelines are intended to give an understanding of a clinical problem and outline one or more preferred approaches to the investigation and management of the problem. The Guidelines are not intended as a substitute for the advice or professional judgment of a health care professional, nor are they intended to be the only approach to the management of clinical problems. We cannot respond to patients or patient advocates requesting advice on issues related to medical conditions. If you need medical advice, please contact a health care professional.